Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin‐1 in macrophages
Abstract
ABSTRACT Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors is the crucial mechanism underlying the suppressive GC effect. Here we demonstrate that mice with a dimerization‐deficient GR (GR dim ) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)‐induced septic shock. TNF‐α is normally regulated in these mice, but down‐regulation of IL‐6 and IL‐1β is diminished. LPS‐treated macrophages derived from GR dim mice are largely resistant to GC actions in vitro in terms of morphology, surface marker expression, and gene expression. Treatment with recombinant IL‐1 receptor antagonist improved survival of GR dim mice and mice lacking the GR in macrophages (GR LysMCre ) mice. This suggests that regulation of IL‐1β in macrophages by GCs is pivotal to control sepsis.—Kleiman, A., Hübner, S., Rodriguez Parkitna, J. M., Neumann, A., Hofer, S., Weigand, M. A., Bauer, M., Schmid, W., Schütz, G., Libert, C., Reichardt, H. M., Tuckermann, J. P. Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin‐1 in macrophages. FASEB J. 26, 722–729 (2012). www.fasebj.org
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Repression of IL-1beta, MIP-2, MCP-1, and IP-10 by GCs is hindered in macrophages isolated from GRdim mice.
“This hypothesis is supported by prior work showing that repression of IL-1β, MIP-2, MCP-1, and IP-10 by GCs is hindered in macrophages isolated from GRdim mice (109, 110).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [109]
Increased mortality was observed in GRlysMCre mice compared to controls following a peripheral injection of LPS.
“Of particular note, increased mortality was also observed in GRlysMCre mice compared to controls following a peripheral injection of LPS (109).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [109]
Cites
Conditional gene targeting in macrophages and granulocytes using LysMcre mice
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R., & Förster, I. (1999) · Transgenic Research · doi:10.1023/a:1008942828960 · Cited by 2,143 · see citing works
The many faces of macrophage activation
Mosser, D. M. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0602325 · Cited by 1,902 · see citing works
Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., Bock, R., Klein, R., & Schütz, G. (1999) · Nature Genetics · doi:10.1038/12703 · Cited by 1,841 · see citing works
DNA binding of the glucocorticoid receptor is not essential for survival
Reichardt, H. M., Kaestner, K. H., Tuckermann, J., Kretz, O., Wessely, O., Bock, R., Gass, P., Schmid, W., Herrlich, P., Angel, P., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81183-6 · Cited by 1,068 · see citing works
Self-citationAnnane, D. (2000) · JAMA · doi:10.1001/jama.283.8.1038 · Cited by 1,000 · see citing works
De Bosscher, K., Vanden Berghe, W., & Haegeman, G. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0006 · Cited by 898 · see citing works
Molecular determinants of crosstalk between nuclear receptors and toll-like receptors
Ogawa, S., Lozach, J., Benner, C., Pascual, G., Tangirala, R. K., Westin, S., Hoffmann, A., Subramaniam, S., David, M., Rosenfeld, M. G., et al. (2005) · Cell · doi:10.1016/j.cell.2005.06.029 · Cited by 647 · see citing works
Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells
Glass, C. K., & Saijo, K. (2010) · Nature Reviews Immunology · doi:10.1038/nri2748 · Cited by 619 · see citing works
Kruppel-like factor 2 regulates thymocyte and T-cell migration
Carlson, C. M., Endrizzi, B. T., Wu, J., Ding, X., Weinreich, M. A., Walsh, E. R., Wani, M. A., Lingrel, J. B., Hogquist, K. A., & Jameson, S. C. (2006) · Nature · doi:10.1038/nature04882 · Cited by 593 · see citing works
Surjit, M., Ganti, K. P., Mukherji, A., Ye, T., Hua, G., Metzger, D., Li, M., & Chambon, P. (2011) · Cell · doi:10.1016/j.cell.2011.03.027 · Cited by 551 · cited 1× · see citing works
“sequences of hormone-responsive target genes (8).”
Abraham, S. M., Lawrence, T., Kleiman, A., Warden, P., Medghalchi, M., Tuckermann, J., Saklatvala, J., & Clark, A. R. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060336 · Cited by 430 · see citing works
Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor
Reichardt, H. M., Tuckermann, J. P., Göttlicher, M., Vujic, M., Weih, F., Angel, P., Herrlich, P., & Schütz, G. (2001) · The EMBO Journal · doi:10.1093/emboj/20.24.7168 · Cited by 429 · see citing works
MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock
Zhao, Q., Wang, X., Nelin, L. D., Yao, Y., Matta, R., Manson, M. E., Baliga, R. S., Meng, X., Smith, C. V., Bauer, J. A., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051794 · Cited by 370 · cited 8× · see citing works
“Among the genes that failed to be induced in GRdim cells by GCs, we found some coding for putative anti-inflammatory factors, such as DUSP-1 (26) and krüppel-like factor 2 (KLF2; ref.”
BackgroundResultInfluentialThe role of the glucocorticoid receptor in inflammation and immunity
Baschant, U., & Tuckermann, J. P. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.03.058 · Cited by 354 · see citing works
Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes
Das, H., Kumar, A., Lin, Z., Patino, W. D., Hwang, P. M., Feinberg, M. W., Majumder, P. K., & Jain, M. K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508235103 · Cited by 305 · see citing works
Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor.
Bertini, R., Bianchi, M., & Ghezzi, P. (1988) · The Journal of experimental medicine · doi:10.1084/jem.167.5.1708 · Cited by 291 · see citing works
Crosstalk between the glucocorticoid receptor and other transcription factors: Molecular aspects
Kassel, O., & Herrlich, P. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.07.003 · Cited by 277 · see citing works
Anti-inflammatory functions of glucocorticoid-induced genes
Clark, A. R. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.04.013 · Cited by 272 · see citing works
Dexamethasone Destabilizes Cyclooxygenase 2 mRNA by Inhibiting Mitogen-Activated Protein Kinase p38
Lasa, M., Brook, M., Saklatvala, J., & Clark, A. R. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.3.771-780.2001 · Cited by 257 · see citing works
Tuckermann, J. P., Kleiman, A., Moriggl, R., Spanbroek, R., Neumann, A., Illing, A., Clausen, B. E., Stride, B., Förster, I., Habenicht, A. J. R., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28034 · Cited by 252 · see citing works
Bhattacharyya, S., Brown, D. E., Brewer, J. A., Vogt, S. K., & Muglia, L. J. (2007) · Blood · doi:10.1182/blood-2006-10-048215 · Cited by 249 · see citing works
Tuckermann, J. P., Kleiman, A., Moriggl, R., Spanbroek, R., Neumann, A., Illing, A., Clausen, B. E., Stride, B. D., Förster, I., Habenicht, A. J. R., et al. (2007) · HAL · Cited by 224 · see citing works
Tuckermann, J. P., Reichardt, H. M., Arribas, R., Richter, K. H., Schütz, G., & Angel, P. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.7.1365 · Cited by 196 · see citing works
Kleiman, A., & Tuckermann, J. P. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.05.009 · Cited by 165 · see citing works
Self-citationPrigent, H., Maxime, V., & Annane, D. (2004) · Critical Care · doi:10.1186/cc2878 · Cited by 151 · see citing works
The GRIP1:IRF3 interaction as a target for glucocorticoid receptor-mediated immunosuppression
Reily, M. M., Pantoja, C., Hu, X., Chinenov, Y., & Rogatsky, I. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600919 · Cited by 149 · see citing works
Adrenal Insufficiency in High-Risk Surgical ICU Patients
Rivers, E. P., Gaspari, M., Mlynarek, M. E., Horst, H., Fath, J. J., Wortsman, J., & Saad, G. A. (2001) · CHEST Journal · doi:10.1378/chest.119.3.889 · Cited by 147 · see citing works
Fluorometric measurement of nitrite/nitrate by 2,3-diaminonaphthalene
Nussler, A. K., Glanemann, M., Schirmeier, A., Liu, L., & Nüssler, N. C. (2006) · Nature Protocols · doi:10.1038/nprot.2006.341 · Cited by 100 · see citing works
Interleukin-1: a gene expression system regulated at multiple levels.
Auron, P. E., & Webb, A. C. (1995) · PubMed · Cited by 94 · see citing works
Wüst, S., Tischner, D., John, M., Tuckermann, J. P., Menzfeld, C., Hanisch, U., van den Brandt, J., Lühder, F., & Reichardt, H. M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008202 · Cited by 80 · see citing works
Differential Regulation of CCL22 Gene Expression in Murine Dendritic Cells and B Cells
Ghadially, H., Ross, X.-L., Kerst, C., Dong, J., Reske‐Kunz, A. B., & Ross, R. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.9.5620 · Cited by 37 · see citing works
Mahony, D., Kalionis, B., & Antalis, T. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00552.x · Cited by 26 · see citing works
Incidence of sepsis in hospitalized patients
Moreno, R. P., Afonso, S., & Fevereiro, T. (2006) · Current Infectious Disease Reports · doi:10.1007/s11908-006-0044-2 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The M1 and M2 paradigm of macrophage activation: Time for reassessment
Martinez, F. O., & Gordon, S. (2014) · F1000Prime Reports · doi:10.12703/p6-13 · Cited by 4,689 · see citing works
Immune regulation by glucocorticoids
Cain, D. W., & Cidlowski, J. A. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.1 · Cited by 1,846 · see citing works
Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa
Dantzer, R. (2018) · Physiological Reviews · doi:10.1152/physrev.00039.2016 · Cited by 1,073 · see citing works
Silverman, M. N., & Sternberg, E. M. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06633.x · Cited by 740 · see citing works
A General Introduction to Glucocorticoid Biology
Timmermans, S., Souffriau, J., & Libert, C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01545 · Cited by 619 · see citing works
Therapeutic Mechanisms of Glucocorticoids
Vandewalle, J., Luypaert, A., Bosscher, K. D., & Libert, C. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.10.010 · Cited by 554 · see citing works
The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain
Bellavance, M.-A., & Rivest, S. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00136 · Cited by 419 · see citing works
Ratman, D., Vanden Berghe, W., Dejager, L., Libert, C., Tavernier, J., Beck, I. M., & De Bosscher, K. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.12.014 · Cited by 411 · see citing works
Self-citationBusillo, J. M., & Cidlowski, J. A. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.11.005 · Cited by 339 · see citing works
Vandevyver, S., Dejager, L., Tuckermann, J., & Libert, C. (2013) · Endocrinology · doi:10.1210/en.2012-2045 · Cited by 296 · see citing works
Catchup: a mouse model for imaging-based tracking and modulation of neutrophil granulocytes
Hasenberg, A., Hasenberg, M., Männ, L., Neumann, F., Borkenstein, L., Stecher, M., Kraus, A., Engel, D. R., Grüneboom, A., Seddigh, P., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3322 · Cited by 280 · see citing works
Therapeutic glucocorticoids: mechanisms of actions in rheumatic diseases
Hardy, R., Raza, K., & Cooper, M. S. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0371-y · Cited by 267 · see citing works
Hartmann, K., Koenen, M., Schauer, S., Wittig-Blaich, S., Ahmad, M., Baschant, U., & Tuckermann, J. P. (2016) · Physiological Reviews · doi:10.1152/physrev.00011.2015 · Cited by 249 · see citing works
Maps and legends: the quest for dissociated ligands of the glucocorticoid receptor
Clark, A. R., & Belvisi, M. G. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.12.004 · Cited by 209 · see citing works
Πέττα, Ι., Dejager, L., Ballegeer, M., Lievens, S., Tavernier, J. H., Bosscher, K. D., & Libert, C. (2016) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00064-15 · Cited by 202 · see citing works
More Than Suppression: Glucocorticoid Action on Monocytes and Macrophages
Ehrchen, J. M., Roth, J., & Barczyk‐Kahlert, K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02028 · Cited by 200 · see citing works
Control of immunity by glucocorticoids in health and disease
Shimba, A., & Ikuta, K. (2020) · Seminars in Immunopathology · doi:10.1007/s00281-020-00827-8 · Cited by 184 · see citing works
New insights into the cell- and tissue-specificity of glucocorticoid actions
Quatrini, L., & Ugolini, S. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00526-2 · Cited by 171 · see citing works
Lim, H., Uhlenhaut, N. H., Rauch, A., Weiner, J., Hübner, S., Hübner, N., Won, K., Lazar, M. A., Tuckermann, J. P., & Steger, D. J. (2015) · Genome Research · doi:10.1101/gr.188581.114 · Cited by 156 · see citing works
New Insights in Glucocorticoid Receptor Signaling—More Than Just a Ligand-Binding Receptor
Scheschowitsch, K., Leite, J. A., & Assreuy, J. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00016 · Cited by 155 · see citing works
Vettorazzi, S., Bode, C., Dejager, L., Frappart, L., Shelest, E., Klaßen, C., Tasdogan, A., Reichardt, H. M., Libert, C., Schneider, M., et al. (2015) · Nature Communications · doi:10.1038/ncomms8796 · Cited by 154 · see citing works
Quatrini, L., Wieduwild, É., Escalière, B., Filtjens, J., Chasson, L., Laprie, C., Vivier, É., & Ugolini, S. (2018) · Nature Immunology · doi:10.1038/s41590-018-0185-0 · Cited by 153 · see citing works
Glucocorticoid receptors: finding the middle ground
Desmet, S. J., & Bosscher, K. D. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88886 · Cited by 149 · see citing works
Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor
Escoter-Torres, L., Caratti, G., Mechtidou, A., Tuckermann, J. P., Uhlenhaut, N. H., & Vettorazzi, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01859 · Cited by 146 · see citing works
The multiple facets of glucocorticoid action in rheumatoid arthritis
Baschant, U., Lane, N. E., & Tuckermann, J. P. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2012.166 · Cited by 138 · see citing works
Glucocorticoid receptor dimerization induces MKP1 to protect against TNF-induced inflammation
Vandevyver, S., Dejager, L., Bogaert, T. V., Kleyman, A., Liu, Y., Tuckermann, J. P., & Libert, C. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60006 · Cited by 133 · see citing works
Glucocorticoids in Sepsis: To Be or Not to Be
Vandewalle, J., & Libert, C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01318 · Cited by 123 · see citing works
Chapman, K. E., Coutinho, A. E., Zhang, Z., Kipari, T. M. J., Savill, J., & Seckl, J. R. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.02.002 · Cited by 118 · see citing works
Endothelial Response to Glucocorticoids in Inflammatory Diseases
Zielińska, K. A., Moortel, L. V., Opdenakker, G., Bosscher, K. D., & den Steen, P. E. V. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00592 · Cited by 116 · see citing works
Xie, Y., Tolmeijer, S. H., Oskam, J. M., Tonkens, T., Meijer, A. H., & Schaaf, M. J. M. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.037887 · Cited by 112 · see citing works
Glucocorticoids Shape Macrophage Phenotype for Tissue Repair
Desgeorges, T., Caratti, G., Mounier, R., Tuckermann, J. P., & Chazaud, B. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01591 · Cited by 102 · see citing works
Sepsis: a failing starvation response
Vandewalle, J., & Libert, C. (2022) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2022.01.006 · Cited by 101 · see citing works
Li, C. C., Munitić, I., Mittelstadt, P. R., Castro, E., & Ashwell, J. D. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002269 · Cited by 99 · see citing works
Clinical Use and Molecular Action of Corticosteroids in the Pediatric Age
Ferrara, G., Petrillo, M. G., Giani, T., Marrani, E., Filippeschi, C., Oranges, T., Simonini, G., & Cimaz, R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020444 · Cited by 97 · see citing works
Mueller, K. M., Themanns, M., Friedbichler, K., Kornfeld, J., Esterbauer, H., Tuckermann, J. P., & Moriggl, R. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.03.026 · Cited by 88 · see citing works
Glucocorticoid resistance as a major drive in sepsis pathology
Dendoncker, K., & Libert, C. (2017) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2017.04.002 · Cited by 85 · see citing works
Ge, Y., Huang, M., & Yao, Y.-M. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.12.004 · Cited by 85 · see citing works
The Role of ACTH and Corticosteroids for Sepsis and Septic Shock: An Update
Annane, D. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00070 · Cited by 83 · see citing works
Novel Drug Delivery Systems Tailored for Improved Administration of Glucocorticoids
Lühder, F., & Reichardt, H. M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091836 · Cited by 80 · see citing works
A macrophage-hepatocyte glucocorticoid receptor axis coordinates fasting ketogenesis
Loft, A., Schmidt, S. F., Caratti, G., Stifel, U., Havelund, J., Sekar, R., Kwon, Y., Sulaj, A., Chow, K. K., Alfaro, A. J., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.004 · Cited by 76 · see citing works
Self-citationCombined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis
Vandewalle, J., Timmermans, S., Paakinaho, V., Vancraeynest, L., Dewyse, L., Vanderhaeghen, T., Wallaeys, C., Wyngene, L. V., Looveren, K. V., Nuyttens, L., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.07.002 · Cited by 78 · see citing works
Langgartner, D., Peterlik, D., Foertsch, S., Füchsl, A. M., Brokmann, P., Flor, P. J., Shen, Z., Fox, J. G., Uschold‐Schmidt, N., Lowry, C. A., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.12.019 · Cited by 72 · see citing works
Glucocorticoid receptor dimers control intestinal STAT1 and TNF-induced inflammation in mice
Ballegeer, M., Looveren, K. V., Timmermans, S., Eggermont, M., Vandevyver, S., Théry, F., Dendoncker, K., Souffriau, J., Vandewalle, J., Wyngene, L. V., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96636 · Cited by 71 · see citing works
Stifel, U., Wolfschmitt, E.-M., Vogt, J. A., Wachter, U. A., Vettorazzi, S., Tews, D., Hogg, M., Zink, F., Koll, N., Winning, S., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101424 · Cited by 73 · see citing works
Activation of the Glucocorticoid Receptor in Acute Inflammation: the SEDIGRAM Concept
Bosscher, K. D., Beck, I. M. E., Ratman, D., Berghe, W. V., & Libert, C. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.09.002 · Cited by 65 · see citing works
Silverman, M. N., Mukhopadhyay, P., Belyavskaya, E., Tonelli, L. H., Revenis, B. D., Doran, J. H., Ballard, B. E., Tam, J., Pacher, P., & Sternberg, E. M. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.131 · Cited by 64 · see citing works
Vettorazzi, S., Nalbantoglu, D., Gebhardt, J. C. M., & Tuckermann, J. P. (2021) · FEBS Journal · doi:10.1111/febs.16100 · Cited by 62 · see citing works
Arthritis and the role of endogenous glucocorticoids
Macfarlane, E., Seibel, M. J., & Zhou, H. (2020) · Bone Research · doi:10.1038/s41413-020-00112-2 · Cited by 64 · see citing works
Ngo, D., Beaulieu, É., Gu, R., Leaney, A., Santos, L. L., Fan, H., Yang, Y., Kao, W., Xu, J., Escriou, V., et al. (2013) · Arthritis & Rheumatism · doi:10.1002/art.37858 · Cited by 61 · see citing works
Quatrini, L., Wieduwild, É., Guia, S., Bernat, C., Glaichenhaus, N., Vivier, É., & Ugolini, S. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20171048 · Cited by 59 · see citing works
Neuroendocrine regulation of innate lymphoid cells
Quatrini, L., Vivier, É., & Ugolini, S. (2018) · Immunological Reviews · doi:10.1111/imr.12707 · Cited by 58 · see citing works
Montes‐Cobos, E., Ring, S., Fischer, H. J., Heck, J. G., Strauß, J., Schwaninger, M., Reichardt, S. D., Feldmann, C., Lühder, F., & Reichardt, H. M. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.12.003 · Cited by 59 · see citing works
Koenen, M., Culemann, S., Vettorazzi, S., Caratti, G., Frappart, L., Baum, W., Krönke, G., Baschant, U., & Tuckermann, J. P. (2018) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2017-212762 · Cited by 59 · see citing works
The glucocorticoid receptor in inflammatory processes: transrepression is not enough
Hübner, S., Dejager, L., Libert, C., & Tuckermann, J. P. (2015) · Biological Chemistry · doi:10.1515/hsz-2015-0106 · Cited by 57 · see citing works
Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model of Allergic Asthma
Klaßen, C., Karabinskaya, A., Dejager, L., Vettorazzi, S., Moorleghem, J. V., Lühder, F., Meijsing, S. H., Tuckermann, J. P., Bohnenberger, H., Libert, C., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601691 · Cited by 54 · see citing works
Meers, G. K., Bohnenberger, H., Reichardt, H. M., Lühder, F., & Reichardt, S. D. (2018) · PLoS ONE · doi:10.1371/journal.pone.0190846 · Cited by 54 · see citing works
Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance
Caratti, G., Stifel, U., Caratti, B., Jamil, A. J. M., Chung, K., Kiehntopf, M., Gräler, M. H., Blüher, M., Rauch, A., & Tuckermann, J. P. (2023) · Nature Communications · doi:10.1038/s41467-023-37831-z · Cited by 50 · see citing works
Wang, X.-Z., Jiang, W., Feng, L., Wu, P., Liu, Y., Zeng, Y.-Y., Jiang, J., Kuang, S., Tang, L., Tang, W., et al. (2018) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2018.04.030 · Cited by 47 · see citing works
Robert, O., Boujedidi, H., Bigorgne, A., Ferrere, G., Voican, C. S., Vettorazzi, S., Tuckermann, J. P., Bouchet‐Delbos, L., Tran, T., Hémon, P., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.023 · Cited by 46 · see citing works
Cheng, Q., Morand, E. F., & Yang, Y. H. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00169 · Cited by 44 · see citing works
Adrenal hormones mediate disease tolerance in malaria
Vandermosten, L., Pham, T., Knoops, S., Geest, C. D., Lays, N., der Molen, K. V., Kenyon, C. J., Verma, M., Chapman, K. E., Schuit, F. C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06986-5 · Cited by 42 · see citing works
Theiss-Suennemann, J., Jörß, K., Messmann, J. J., Reichardt, S. D., Montes‐Cobos, E., Lühder, F., Tuckermann, J. P., AWolff, H., Dressel, R., Gröne, H., et al. (2014) · The Journal of Pathology · doi:10.1002/path.4475 · Cited by 41 · see citing works
GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life
Louw, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01693 · Cited by 42 · see citing works
Improved Glucocorticoid Receptor Ligands: Fantastic Beasts, but How to Find Them?
Moortel, L. V., Gevaert, K., & Bosscher, K. D. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.559673 · Cited by 41 · see citing works
Lipid oxidation dysregulation: an emerging player in the pathophysiology of sepsis
Muniz‐Santos, R., Costa, G. L. A., de Almeida, M. A. P., Moraes-de-Souza, I., Brito, M. A. D. S. M., Silva, A. R., & Gonçalves-de-Albuquerque, C. F. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1224335 · Cited by 41 · see citing works
Adrenocortical Stress Response during the Course of Critical Illness
Peeters, B., Langouche, L., & den Berghe, G. V. (2017) · Comprehensive physiology · doi:10.1002/cphy.c170022 · Cited by 43 · see citing works
Glucocorticoid‐induced microRNA‐511 protects against TNF by down‐regulating TNFR1
Puimège, L., Hauwermeiren, F. V., Steeland, S., Ryckeghem, S. V., Vandewalle, J., Lodens, S., Dejager, L., Vandevyver, S., Staelens, J., Timmermans, S., et al. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201405010 · Cited by 37 · see citing works
Haffa, M., Holowatyj, A. N., Kratz, M., Tóth, R., Benner, A., Gigic, B., Habermann, N., Schrotz‐King, P., Böhm, J., Brenner, H., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00461 · Cited by 36 · see citing works
The Management of Glucocorticoid Therapy in Liver Failure
Xue, R., & Meng, Q. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02490 · Cited by 36 · see citing works
Fischer, H. J., Schweingruber, N., Lühder, F., & Reichardt, H. M. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.04.001 · Cited by 34 · see citing works
Greulich, F., Hemmer, M. C., Rollins, D. A., Rogatsky, I., & Uhlenhaut, N. H. (2016) · Steroids · doi:10.1016/j.steroids.2016.05.003 · Cited by 34 · see citing works
Baumeister, D., Lightman, S. L., & Pariante, C. M. (2016) · Psychopathology Review · doi:10.5127/pr.034413 · Cited by 32 · see citing works
Montes‐Cobos, E., Schweingruber, N., Li, X., Fischer, H. J., Reichardt, H. M., & Lühder, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01319 · Cited by 32 · see citing works
Scavenger Receptor BI and High-Density Lipoprotein Regulate Thymocyte Apoptosis in Sepsis
Guo, L., Zheng, Z., Ai, J., Howatt, D. A., Mittelstadt, P. R., Thacker, S. G., Daugherty, A., Ashwell, J. D., Remaley, A. T., & Li, X. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.302484 · Cited by 32 · see citing works
Eiers, A.-K., Vettorazzi, S., & Tuckermann, J. P. (2024) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2023-225371 · Cited by 31 · see citing works
Gruber, A., Müller, R., Wagner, A., Colucci, S., Spasić, M. V., & Leopold, K. (2020) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-020-02614-8 · Cited by 30 · see citing works
Liu, Y., Yu, Y., Liu, J., Liu, W., Cao, Y., Yan, R., & Yao, Y. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.892480 · Cited by 30 · see citing works
Induced global deletion of glucocorticoid receptor impairs fracture healing
Rapp, A. E., Hachemi, Y., Kemmler, J., Koenen, M., Tuckermann, J. P., & Ignatius, A. A. (2017) · The FASEB Journal · doi:10.1096/fj.201700459rr · Cited by 29 · see citing works
Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer
Timmermans, S., Vandewalle, J., & Libert, C. (2022) · Cells · doi:10.3390/cells11040683 · Cited by 29 · see citing works
Sasse, S. K., Altonsy, M. O., Kadiyala, V., Cao, G., Panettieri, R. A., & Gerber, A. N. (2016) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00179.2016 · Cited by 28 · see citing works
Molecular determinants of glucocorticoid actions in inflammatory joint diseases
Baschant, U., Culemann, S., & Tuckermann, J. P. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.06.009 · Cited by 28 · see citing works
Wepler, M., Preuss, J. M., Merz, T., Hartmann, C., Wachter, U. A., McCook, O., Vogt, J. A., Kress, S., Gröger, M., Fink, M., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03152 · Cited by 26 · see citing works
Merz, T., Denoix, N., Wigger, D., Waller, C., Wepler, M., Vettorazzi, S., Tuckermann, J. P., Radermacher, P., & McCook, O. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00299 · Cited by 26 · see citing works
Ai, J., Guo, L., Zheng, Z., Wang, S., Huang, B., & Li, X. (2015) · Critical Care Medicine · doi:10.1097/ccm.0000000000001264 · Cited by 22 · see citing works
Pfänder, P., Fidan, M., Burret, U., Lipinski, L., & Vettorazzi, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01554 · Cited by 24 · see citing works
Souffriau, J., Eggermont, M., Ryckeghem, S. V., Looveren, K. V., Wyngene, L. V., Hamme, E. V., Vuylsteke, M., Beyaert, R., Bosscher, K. D., & Libert, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-31150-w · Cited by 23 · see citing works
A Jack of All Trades: Impact of Glucocorticoids on Cellular Cross-Talk in Osteoimmunology
Ahmad, M., Hachemi, Y., Paxian, K., Mengele, F., Koenen, M., & Tuckermann, J. P. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02460 · Cited by 22 · see citing works
Steroid hormone regulation of immunometabolism and inflammation
Smith, L. C., Ramar, M., Riley, G., Mathias, C. B., & Lee, J.-Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1654034 · Cited by 25 · see citing works
Baake, T., Jörß, K., Theiss-Suennemann, J., Roßmann, L., Bohnenberger, H., Tuckermann, J. P., Reichardt, H. M., Fischer, H. J., & Reichardt, S. D. (2018) · Oncotarget · doi:10.18632/oncotarget.24602 · Cited by 21 · see citing works
Moortel, L. V., Thommis, J., Maertens, B., Staes, A., Clarisse, D., Sutter, D. D., Libert, C., Meijer, O. C., Eyckerman, S., Gevaert, K., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113218 · Cited by 19 · see citing works
Coons, L. A., Hewitt, S. C., Burkholder, A., McDonnell, D. P., & Korach, K. S. (2017) · Endocrinology · doi:10.1210/en.2017-00468 · Cited by 20 · see citing works
Reprogramming of glucocorticoid receptor function by hypoxia
Vanderhaeghen, T., Timmermans, S., Watts, D., Paakinaho, V., Eggermont, M., Vandewalle, J., Wallaeys, C., Wyngene, L. V., Looveren, K. V., Nuyttens, L., et al. (2021) · EMBO Reports · doi:10.15252/embr.202153083 · Cited by 17 · see citing works
Ronaghan, N. J., Soo, M., Pena, U., Tellis, M., Duan, W., Tabatabaei-Zavareh, N., Kramer, P., Hou, J., & Moraes, T. J. (2022) · PLoS ONE · doi:10.1371/journal.pone.0276013 · Cited by 18 · see citing works
Bergquist, M., Lindholm, C., Strinnholm, M., Hedenstierna, G., & Rylander, C. C. (2015) · Intensive Care Medicine Experimental · doi:10.1186/s40635-015-0059-9 · Cited by 18 · see citing works
Wepler, M., Preuss, J. M., Merz, T., McCook, O., Radermacher, P., Tuckermann, J. P., & Vettorazzi, S. (2020) · Intensive Care Medicine Experimental · doi:10.1186/s40635-020-00325-z · Cited by 17 · see citing works
Escoll, P., Ranz, I., Muñoz-Antón, N., Rym, A. M. V. D., Álvarez‐Mon, M., Martínez-Alonso, C., Sanz, E., & de-la-Hera, A. (2015) · Mediators of Inflammation · doi:10.1155/2015/347965 · Cited by 16 · see citing works
Glucocorticoids limit lipopolysaccharide‐induced lethal inflammation by a double control system
Looveren, K. V., Timmermans, S., Vanderhaeghen, T., Wallaeys, C., Ballegeer, M., Souffriau, J., Eggermont, M., Vandewalle, J., Wyngene, L. V., Bosscher, K. D., et al. (2020) · EMBO Reports · doi:10.15252/embr.201949762 · Cited by 15 · see citing works
Correlations between ACE single nucleotide polymorphisms and prognosis of patients with septic shock
Dou, X., Cheng, H., Meng, L., Zhou, L., Ke, Y.-H., Liu, L., & Li, Y. (2017) · Bioscience Reports · doi:10.1042/bsr20170145 · Cited by 15 · see citing works
Kaiser, T. K., Khorenko, M., Moussavi, A., Engelke, M., Boretius, S., Feldmann, C., & Reichardt, H. M. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.01.010 · Cited by 14 · see citing works
Does Stress-Induced Release of Interleukin-1 Cause Liver Injury?
Цейликман, В. Э., Kozochkin, D. A., Synitsky, A., Sibiriak, S., Tseilikman, O. B., Katashinsky, E., Nikitina, A., Vinogradov, D., & Simbirtsev, A. S. (2012) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-012-9866-7 · Cited by 14 · see citing works
- Authors
- Kleiman, A., Hübner, S., Parkitna, J. M. R., Neumann, A., Hofer, S., Weigand, M. A., Bauer, M., Schmid, W., Schütz, G., Libert, C., Reichardt, H. M., & Tuckermann, J. P.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- Justus-Liebig-Universität Gießen (DE)
- Jena University Hospital (DE)
- Vlaams Instituut voor Biotechnologie (BE)
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Tuckermann, Jan P.
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2011-10-31
- Volume
- 26
- Issue
- 2
- Pages
- 722-729
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2066022850
- Cited by
- 152
- References
- 33
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 10 · 2020: 14 · 2019: 16 · 2018: 16 · 2017: 16 · 2016: 10 · 2015: 14 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 6.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- GRO (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Tu220/3, Re1631/7-1)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- glucocorticoid receptor, receptor dimerization, septic shock, sepsis, IL-1β, macrophages, lipopolysaccharide, cecal ligation and puncture, interleukin-6, TNF-α, interleukin-1 receptor antagonist, glucocorticoid resistance, endogenous glucocorticoids
- MeSH terms
- Animals, Dexamethasone, Disease Models, Animal, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Receptors, Glucocorticoid, RNA, RNA, Messenger, Shock, Septic, Tumor Necrosis Factor-alpha, Signal Transduction, Down-Regulation, Interleukin-6, Receptors, Interleukin-1, Dimerization, Protein Structure, Quaternary, Mice, Interleukin-1beta, Mice, 129 Strain, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
